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Metastasis of breast cancer to bones alters the tumor immune microenvironment
BACKGROUND: Bone is one of the most frequent sites for breast cancer metastasis. Breast cancer bone metastasis (BCBM) leads to skeletal morbidities including pain, fractures, and spinal compression, all of which severely impact quality of life. Immunotherapy is a promising therapy for patients with...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012464/ https://www.ncbi.nlm.nih.gov/pubmed/36915210 http://dx.doi.org/10.1186/s40001-023-01083-w |
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author | Chao, Xue Zhang, Ying Zheng, Chengyou Huang, Qitao Lu, Jiabin Pulver, Emilia M. Houthuijzen, Julia Hutten, Stefan Luo, Rongzhen He, Jiehua Sun, Peng |
author_facet | Chao, Xue Zhang, Ying Zheng, Chengyou Huang, Qitao Lu, Jiabin Pulver, Emilia M. Houthuijzen, Julia Hutten, Stefan Luo, Rongzhen He, Jiehua Sun, Peng |
author_sort | Chao, Xue |
collection | PubMed |
description | BACKGROUND: Bone is one of the most frequent sites for breast cancer metastasis. Breast cancer bone metastasis (BCBM) leads to skeletal morbidities including pain, fractures, and spinal compression, all of which severely impact quality of life. Immunotherapy is a promising therapy for patients with advanced cancer, but whether it may provide benefit to metastatic bone cancer is currently unknown. Thus, a better understanding of the immune landscape of bone-disseminated breast cancers may reveal new therapeutic strategies. In this study, we use histopathological analysis to investigate changes within the immune microenvironment of primary breast cancer and paired BCBM. METHODS: Sixty-three patients with BCBM, including 31 with paired primary and bone metastatic lesions, were included in our study. The percentage of stroma and stromal tumor-infiltrating lymphocytes (TILs) was evaluated by histopathological analysis. The quantification of stromal TILs (CD4 + and CD8 +), macrophages (CD68 + and HLA-DR +), programmed cell death protein 1 (PD-1), and programmed cell death protein ligand 1 (PD-L1) was evaluated through immunohistochemical (IHC) staining. Statistical analysis was performed with paired t test, Wilcoxon test, spearman correlation test, and univariate and multivariate cox regression. RESULTS: Median survival after BCBM pathological diagnosis was 20.5 months (range: 3–95 months). Of the immune parameters measured, none correlated with survival after bone metastasis was diagnosed. Compared to the primary site, bone metastases exhibited more tumor stroma (mean: 58.5% vs 28.87%, p < 0.001) and less TILs (mean: 8.45% vs 14.03%, p = 0.042), as determined by H&E analysis. The quantification of primary vs metastatic tissue area with CD4 + (23.95/mm(2) vs 51.69/mm(2), p = 0.027 and with CD8 + (18.15/mm(2) vs 58.95/mm(2), p = 0.004) TILs similarly followed this trend and was reduced in number for bone metastases. The number of CD68 + and HLA-DR + macrophages showed no significant difference between primary sites and bone metastases. PD-1 expression was present in 68.25% of the bone metastasis, while PD-L1 expression was only present in 7.94% of the bone metastasis. CONCLUSIONS: Our findings suggest that compared to the primary breast cancer site, bone metastases harbor a less active immune microenvironment. Despite this relatively dampened immune landscape, expression of PD-1 and PD-L1 in the bone metastasis indicates a potential benefit from immune checkpoint inhibitors for some BCBM cases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40001-023-01083-w. |
format | Online Article Text |
id | pubmed-10012464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100124642023-03-15 Metastasis of breast cancer to bones alters the tumor immune microenvironment Chao, Xue Zhang, Ying Zheng, Chengyou Huang, Qitao Lu, Jiabin Pulver, Emilia M. Houthuijzen, Julia Hutten, Stefan Luo, Rongzhen He, Jiehua Sun, Peng Eur J Med Res Research BACKGROUND: Bone is one of the most frequent sites for breast cancer metastasis. Breast cancer bone metastasis (BCBM) leads to skeletal morbidities including pain, fractures, and spinal compression, all of which severely impact quality of life. Immunotherapy is a promising therapy for patients with advanced cancer, but whether it may provide benefit to metastatic bone cancer is currently unknown. Thus, a better understanding of the immune landscape of bone-disseminated breast cancers may reveal new therapeutic strategies. In this study, we use histopathological analysis to investigate changes within the immune microenvironment of primary breast cancer and paired BCBM. METHODS: Sixty-three patients with BCBM, including 31 with paired primary and bone metastatic lesions, were included in our study. The percentage of stroma and stromal tumor-infiltrating lymphocytes (TILs) was evaluated by histopathological analysis. The quantification of stromal TILs (CD4 + and CD8 +), macrophages (CD68 + and HLA-DR +), programmed cell death protein 1 (PD-1), and programmed cell death protein ligand 1 (PD-L1) was evaluated through immunohistochemical (IHC) staining. Statistical analysis was performed with paired t test, Wilcoxon test, spearman correlation test, and univariate and multivariate cox regression. RESULTS: Median survival after BCBM pathological diagnosis was 20.5 months (range: 3–95 months). Of the immune parameters measured, none correlated with survival after bone metastasis was diagnosed. Compared to the primary site, bone metastases exhibited more tumor stroma (mean: 58.5% vs 28.87%, p < 0.001) and less TILs (mean: 8.45% vs 14.03%, p = 0.042), as determined by H&E analysis. The quantification of primary vs metastatic tissue area with CD4 + (23.95/mm(2) vs 51.69/mm(2), p = 0.027 and with CD8 + (18.15/mm(2) vs 58.95/mm(2), p = 0.004) TILs similarly followed this trend and was reduced in number for bone metastases. The number of CD68 + and HLA-DR + macrophages showed no significant difference between primary sites and bone metastases. PD-1 expression was present in 68.25% of the bone metastasis, while PD-L1 expression was only present in 7.94% of the bone metastasis. CONCLUSIONS: Our findings suggest that compared to the primary breast cancer site, bone metastases harbor a less active immune microenvironment. Despite this relatively dampened immune landscape, expression of PD-1 and PD-L1 in the bone metastasis indicates a potential benefit from immune checkpoint inhibitors for some BCBM cases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40001-023-01083-w. BioMed Central 2023-03-13 /pmc/articles/PMC10012464/ /pubmed/36915210 http://dx.doi.org/10.1186/s40001-023-01083-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Chao, Xue Zhang, Ying Zheng, Chengyou Huang, Qitao Lu, Jiabin Pulver, Emilia M. Houthuijzen, Julia Hutten, Stefan Luo, Rongzhen He, Jiehua Sun, Peng Metastasis of breast cancer to bones alters the tumor immune microenvironment |
title | Metastasis of breast cancer to bones alters the tumor immune microenvironment |
title_full | Metastasis of breast cancer to bones alters the tumor immune microenvironment |
title_fullStr | Metastasis of breast cancer to bones alters the tumor immune microenvironment |
title_full_unstemmed | Metastasis of breast cancer to bones alters the tumor immune microenvironment |
title_short | Metastasis of breast cancer to bones alters the tumor immune microenvironment |
title_sort | metastasis of breast cancer to bones alters the tumor immune microenvironment |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012464/ https://www.ncbi.nlm.nih.gov/pubmed/36915210 http://dx.doi.org/10.1186/s40001-023-01083-w |
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